CD34+ myeloma cells with self-renewal activities are therapy-resistant and persist as MRD in cell cycle quiescence.
CD34+ myeloma cells with self-renewal activities are therapy-resistant and persist as MRD in cell cycle quiescence.
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具有自我更新活性的 CD34+ 骨髓瘤细胞具有治疗抵抗性，并且在细胞周期静止中持续存在 MRD。
DOI：
10.1007/s12185-021-03261-0
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发表时间：
2022
期刊：
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通讯作者：
Serizawa K; Tanaka H; Ueda T; Fukui A; Kakutani H; Taniguchi T; Inoue H; Kumode T; Taniguchi Y; Rai S; Hirase C; Morita Y; Espinoza JL; Tatsumi Y; Ashida T; Matsumura I
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作者：
Bell Katharina;Mori Kazuhiko;lkeda Yoko;Nakano Masakazu;Ueno Morio;Kinoshita Shigeru;Tashiro Kei;Sotozono Chie;Aung Tin et al.;Serizawa K; Tanaka H; Ueda T; Fukui A; Kakutani H; Taniguchi T; Inoue H; Kumode T; Taniguchi Y; Rai S; Hirase C; Morita Y; Espinoza JL; Tatsumi Y; Ashida T; Matsumura I
已知侧群（SP）包括各种癌症中的治疗耐药细胞。在这里，我们使用多发性骨髓瘤（MM）样本分析SP。SP在新发MM (NDMM) MM细胞中占2.96%。CD34在47.8%的SP细胞中表达，而在大体积MM细胞中仅表达2.11%。CD34+MM细胞比CD34−MM细胞表达更多的未成熟细胞表面标记物和基因特征。在异种移植实验中，CD34+而非CD34−MM细胞具有克隆生成活性，并表现出长期的自我更新活性。同样，在NDMM中，有2.20%的MM细胞是CD34+ (n= 38)，而在微小残留病（MRD）样本中，这一比例增加到42.6% (n= 16) (p< 0.001)，在难治性/复发性MM （RRMM）样本中，这一比例增加到17.7% (n= 30) （p< 0.01）。细胞周期分析显示，来自NDMM的CD34+MM细胞中有24.7%处于G0期，而在MRD中这一比例为54.9% (p< 0.05)，在RRMM中这一比例为14.5%，反映了MM的扩增。总之，具有长期自我更新活性的CD34+MM细胞在细胞周期静止期作为MRD存在，或在RRMM中仍作为耐药细胞存在，证实了针对这一群体改善MM临床结果的必要性。
Side population (SP) is known to include therapy-resistant cells in various cancers. Here, we analyzed SP using multiple myeloma (MM) samples. The SP accounted for 2.96% in MM cells from newly diagnosed MM (NDMM). CD34 was expressed in 47.8% of SP cells, but only in 2.11% of bulk MM cells. CD34+MM cells expressed more immature cell surface markers and a gene signature than CD34−MM cells. CD34+but not CD34−MM cells possessed clonogenic activities and showed long-term self-renewal activities in xenotransplantation assays. Similarly, whereas 2.20% of MM cells were CD34+in NDMM (n= 38), this proportion increased to 42.6% in minimal residual disease (MRD) samples (n= 16) (p< 0.001) and to 17.7% in refractory/relapsed MM (RRMM) (n= 30) (p< 0.01). Cell cycle analysis showed that 24.7% of CD34+MM cells from NDMM were in G0 phase while this proportion was 54.9% in MRD (p< 0.05) and 14.5% in RRMM, reflecting the expansion of MM. Together, CD34+MM cells with long-term self-renewal activities persist as MRD in cell cycle quiescence or remain as therapy-resistant cells in RRMM, substantiating the necessity of targeting this population to improve clinical outcomes of MM.